The present invention relates to a process for the combinatorial production of material libraries and testing of the same using at least two analytical methods and to an apparatus for carrying out this process.
Combinatorial methods have been for some time the centre of interest of research and development in the field of material research. Using these combinatorial methods, as great a number as possible of different or identical chemical compounds are always prepared and thus a material library is produced which are then investigated for useful properties using a suitable method. In addition to magnetic, electronic, electromagnetic, optical, electrooptical, electromechanical properties etc., interest also centres on catalytical properties of such materials prepared by combinatorial or highly parallel methods. In this context we refer to WO 99/41005 and the prior art cited therein. This publication relates to arrays of heterogeneous catalysts and/or their precursors, built up from a body which has preferably parallel continuous channels and in which at least n channels contain n different heterogeneous catalysts and/or their precursors, where n has the value 2, preferably 10, particularly preferably 100, in particular 1000, especially 10,000. Furthermore, the publication relates to a process for preparing such arrays and to a process for determining the activity, selectivity and/or long-term stability of catalysts in such an array.
Relatively large material libraries can be studied simply by analysing the heat produced in the reaction. According to WO 97/32208, WO 98/15813 and Ind. Eng. Chem. Res. 1996, 35, pp. 4801-4803, an entire material library is studied for its useful properties using a thermosensitive camera. The disadvantage of the method is essentially that the thermosensitive camera reflects via the heat liberated only the degree of activity of the catalysts. For a number of reactions this information is sufficient (total oxidations, complete hydrations etc.) (see, inter alia, Holzwarth, A., Schmidt, H. W., Maier, W. F., Angewandte Chemie, 1998, 110, 19, 2788-2791; Reetz, M. T., Becker, M. H., Holzwarth, A., Angewandte Chemie, 1998, 110, 19, 2792-2795), but in other reactions, especially what are termed partial oxidations of hydrocarbons, to evaluate catalytic properties of a building block of a material library information on activity alone is not sufficient, since the selectivity of the building block in such reaction types generally plays a greater role than the activity.
WO 97/32208 refers in general terms without a more detailed disclosure to the fact that the detector of the apparatus can further comprise Raman spectroscopy, FT-IR spectroscopy, NMR, mass spectroscopy, gas chromatography, liquid chromatography and enzymatic or biological additions, etc.
Mass spectrometry, owing to its high sensitivity, has long occupied a position in the field of organic and pharmaceutical combinatorial chemistry. Recent work by Weinberg et al. demonstrates the possibility of employing mass spectrometric methods for high-speed screening of heterogeneous catalyst libraries (P. Cong, R. D. Doolen, Q. Fan, D. M. Giaqunta, S. Guan, E. W. McFarland, D. M. Poojary, K. Self, H. W. Turner, W. H. Weinberg, Angew. Chem. 111 (1999) 507; U.S. Pat. No. 5,959,297, WO 98/15969 A2, W. H. Weinberg, E. W. McFarland, P. Gong, S. Guan, Symyx Technologies, 1998; R. F. Service, Science 280 (1998) 1690). Weinberg and collaborators detect the CO2 formed and the starting gases by mass spectrometry in the oxidation of CO by O2 or NO on metal alloys of Rh, Pd, Pt and Cu. For this purpose they use a capillary bundle for spatially separated starting material feed and product removal in the form of a quartz capillary which is coupled to a mass spectrometer. Taking into account the method of synthesizing ternary metal alloys via radiofrequency cathode atomization and the use of various mask systems (U.S. Pat. Nos. 5,985,356, 6,004,617, WO96/11878, P. G. Schultz, X. Xiang, I. Goldwasser, Symyx Technologies, 1996), it can be seen how the above-cited patent literature also describes that the actual structure is much more complicated than the very schematic description in the publications. For catalyst amounts of from 2 to 4 μg on a catalyst element of 1.5 mm in diameter, even at conversion rates of from 80 to 90% and high selectivities, as is the case in the oxidation of CO, only very small amounts of product are formed. Thus a complex modification of the mass spectrometer with a second quadrupole mask (“ion guide”) and the construction of a vacuum chamber system for separate analysis, sample pretreatment and actual testing are required. Especially, handling samples from the outside is made much more difficult. In this example also differentiation can actually only be via catalyst activities, the oxidation of CO by O2 or NO to form CO2 as the sole possible reaction product provides no information on the selectivity differences in the individual library members. In more complex reactions having a plurality of possible products which are frequently formed at low yields with different or similar selectivities, this method fails owing to the too small amounts of product.
Overall, the method of Weinberg et al. requires high financial expenditure and much equipment. The conditions of the catalytic testing and catalyst production must be termed highly idealized and remote from industrially relevant conditions. The applicability and use of the results obtained on a laboratory scale is questionable. Overall, the method demonstrates, however, the applicability in principle of mass spectrometry in combinatorial solid-state research.
In addition to Symyx, Maier and collaborators also describe a system for the mass-spectrometric scanning of libraries of heterogeneous catalysts (M. Orschel, J. Klein, W. F. Maier, Angewandte Chemie, 1999, 111, 18, 2961). This very simple process for the spatially resolved determination of catalytic activities and selectivities using mass spectrometry results from coupling an automated synthesis machine to a commercial gas analyser. It is shown that using a suitable arrangement of feed and measuring capillaries different selectivities of heterogeneously catalysed reactions on a catalyst library open to the outside can be reliably and rapidly studied in a spatially resolved manner. Using as example the selective oxidation of propene with atmospheric oxygen at temperatures of from 250 to 450° C., the selective formations of acrolein, benzene and 1,5-hexadiene may be assigned to different catalyst materials. This arrangement is characterized by the use of relatively large amounts of catalyst (from 1 to 2 mg) in contrast to Symyx and by the fact that an open system is employed (operating under atmospheric pressure, generation of “microreactors” by attaching a capillary bundle of starting material feed and product removal). However, in this case also the overflow principle corresponds only remotely to actual reaction conditions resembling those in industry. If a large material library is scanned completely, the time factor due to the sequential measurement of each individual measuring building block is virtually unacceptable; in addition, the catalysts, owing to the integral heating of the overall library, are exposed to very different thermal conditions depending on whether they are tested at the beginning or at the end of a run. In comparison with parallel simultaneous recording of an entire library in IR thermography, mass-spectrometric sequential scanning must be classified as a very slow method. On p. 2965 at the end of this article there is also a reference to the possibility of combining mass spectrometry and IR thermography without any details being disclosed in this regard.